Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort

Research output: Contribution to journalArticle

Abstract

Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination.

Details

Authors
  • Renée T Fortner
  • Anika Hüsing
  • Tilman Kühn
  • Meric Konar
  • Kim Overvad
  • Anne Tjønneland
  • Louise Hansen
  • Marie-Christine Boutron-Ruault
  • Gianluca Severi
  • Agnès Fournier
  • Heiner Boeing
  • Antonia Trichopoulou
  • Vasiliki Benetou
  • Philippos Orfanos
  • Giovanna Masala
  • Claudia Agnoli
  • Amalia Mattiello
  • Rosario Tumino
  • Carlotta Sacerdote
  • H. Bas Bueno-de-Mesquita
  • Petra H. M. Peeters
  • Elisabete Weiderpass
  • Inger T Gram
  • Oxana Gavrilyuk
  • J Ramón Quirós
  • José Maria Huerta
  • Eva Ardanaz
  • Nerea Larrañaga
  • Leila Lujan-Barroso
  • Emilio Sánchez-Cantalejo
  • Annika Idahl
  • Eva Lundin
  • Kay Tee Khaw
  • Naomi E Allen
  • Sabina Rinaldi
  • Laure Dossus
  • Marc Gunter
  • Melissa A Merritt
  • Ioanna Tzoulaki
  • Elio Riboli
  • Rudolf Kaaks
Organisations
External organisations
  • German Cancer Research Centre
  • Aarhus University
  • Danish Cancer Society Research Center
  • Centre for Research in Epidemiology and Population Health (CESP)
  • University of Paris-Sud
  • Stabilite genetique et oncogenese
  • Human Genetics Foundation (HuGeF)
  • German Institute of Human Nutrition
  • Hellenic Health Foundation, Athens
  • National and Kapodistrian University of Athens
  • Cancer Research and Prevention Institute (ISPO)
  • Istituto Nazionale dei Tumori
  • University of Naples Federico II
  • Civic and M.P Arezzo Hospital
  • Citta' della Salute e della Scienza Hospital-University of Turin
  • National Institute for Public Health and the Environment (RIVM)
  • Imperial College London
  • University of Malaya
  • University Medical Center Utrecht
  • Cancer Registry of Norway, Institute of Population-Based Cancer Research
  • Karolinska Institutet
  • Folkhälsan Research Center
  • University Hospital of North Norway
  • Public Health Directorate
  • Murcia Regional Health Council
  • Public Health Division of Gipuzkoa
  • Bellvitge Biomedical Research Institute
  • Instituto de Investigación Biosanitaria de Granada (Granada.ibs)
  • Umeå University
  • University of Cambridge
  • University of Oxford
  • International Agency for Research on Cancer, World Health Organization
  • Health Research Institute of Navarra (IDISNA)
  • Hacettepe University
  • UiT The Arctic University of Norway, Tromsø
  • CIBER Epidemiology and Public Health (CIBERESP)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • adipokines, cytokines, endometrial cancer, growth factors, inflammatory markers, lipids, metabolic markers, prospective cohort, risk prediction, sex steroids
Original languageEnglish
Pages (from-to)1317-1323
Number of pages7
JournalInternational Journal of Cancer
Volume140
Issue number6
Publication statusPublished - 2017 Mar 15
Publication categoryResearch
Peer-reviewedYes